augmented response of volatile biomarkers in assessment of oesophagogastric cancer (aroma 1 / bioresource)

Conditions: Volatile Organic Compounds; Microbiome; Microbioata; Breath Analysis; Oesophageal Cancer; Gastric Cancer; Volatalomics; Metabonomics/Lipidomics; Microbiome Analysis; Transcriptomics

Summary: cancer of the stomach and oesophagus is among the world's top five cancers. survival rates are very poor as the disease presents late and early symptoms are non-specific. the study team has developed a non-invasive test for cancers of the stomach and oesophagus based on the detection of volatile organic compounds in exhaled breath. these compounds are known to be produced by both cancers as well as cancer associated bacteria within the gut. the proposed innovation is to improve the accuracy of this test by investigating whether simple metabolic substrates can increase the production of these volatile organic compounds by both the tumour and its associated bacteria.

aroma 1: a total of 648 patients will be recruited for development of an augmented breath test to detect oesophageal and gastric cancer at early stages of disease. three groups, each containing 216 patients, will be recruited: (i) oesophageal cancer (ii) gastric cancer and (iii) control/normal patients with upper gastrointestinal symptoms. after a baseline breath sample is collected, subjects will then be asked to consume a standard nutrient drink. further breath samples will be collected at 0 and 15 minutes after consumption of the drink. breath samples will be stored on thermal desportion tubes before being transfered to a central laboratory for analysis. breath samples will be analysed in accordance with existing quality-controlled processes. a combined approach of chromatographic- and real time- mass spectrometric techniques will be applied for voc profiling. bioresource: samples from 335 patients will be collected in order to establish a biobank for multi-omic analyses. three groups, each containing 75 patients, will be recruited: (i) oesophageal adenocarcinoma; (ii) gastric adenocarcinoma and (iii) oesophageal controls - benign conditions/normal gastrointestinal tract with upper gastrointestinal symptoms (iv) gastric controls - benign conditions/normal gastrointestinal tract with upper gastrointestinal symptoms. the following biosamples will be collected: breath, urine, saliva, blood, tissue and gastric contents. collected samples will be utilised in a wide range of studies to investigate the mechanisms of voc production in cancer. the following analyses will be performed: volatalomics, metabonomics/lipidomics, microbiome analysis, transcriptomics and cell culture experiments.

Eligibility criteria:
aroma 1 inclusion criteria: 1. aged 18-90years 2. oesophageal/gastric cancer cohort: participants with biopsy proven adenocarcinoma who are treatment naïve 3. control cohort: participants with normal or benign upper gastrointestinal disease determined on: • endoscopy within 1 year • planned endoscopy aroma 1 exclusion criteria: patients with the following characteristics will not be eligible for inclusion in this study: 1. oesophageal squamous cell carcinoma 2. previous oesophageal and gastric resection 3. received neoadjuvant chemotherapy for oesophageal or gastric cancer 4. history of another cancer within three years 5. any form of oesophageal dysplasia (control cohort only) 6. previously diagnosed with barrett's oesophagus (control cohort only) 7. active infection, on immunosuppressive medications or antibiotic therapy within the last 8 weeks 8. participants with co-morbidities preventing breath collection 9. allergies to any of the constituents of the nutrient drink including glucose, glycerol, iron sulphate, maltodextrin (corn, potato), xanthan gum, potassium chloride, tyrosine, phenylalanine, and glutamic acid 10. unable or unwilling to provide informed written consent 11. pregnant participants bioresource inclusion criteria: 1. aged 18- 90years 2. oesophageal/gastric cancer cohort: participants with biopsy proven adenocarcinoma who are treatment naïve 3. oesophageal/gastric control cohort: participants with normal or benign upper gastrointestinal disease determined on: • planned endoscopy bioresource exclusion criteria: 1. oesophageal squamous cell carcinoma 2. previous oesophageal and gastric resection 3. received neoadjuvant chemotherapy for oesophageal or gastric cancer 4. history of another cancer within five years 5. any form of oesophageal dysplasia (oesophageal/gastric control cohorts only) 6. previously diagnosed with barrett's oesophagus (oesophageal/gastric control cohorts only) 7. active infection, on immunosuppressive medications or antibiotic therapy within the last 8 weeks 8. participants with co-morbidities preventing breath collection 9. unable or unwilling to provide informed written consent 10. pregnant participants